title: The antibacterial threaded-lasso peptide capistruin inhibits bacterial RNA polymerase.
abstract: Capistruin, a ribosomally synthesized, post-translationally modified peptide produced by Burkholderia thailandensis E264, efficiently inhibits growth of Burkholderia and closely related Pseudomonas strains. The functional target of capistruin is not known. Capistruin is a threaded-lasso peptide (lariat peptide) consisting of an N-terminal ring of nine amino acids and a C-terminal tail of 10 amino acids threaded through the ring. The structure of capistruin is similar to that of microcin J25 (MccJ25), a threaded-lasso antibacterial peptide that is produced by some strains of Escherichia coli and targets DNA-dependent RNA polymerase (RNAP). Here, we show that capistruin, like MccJ25, inhibits wild type E. coli RNAP but not mutant, MccJ25-resistant, E. coli RNAP. We show further that an E. coli strain resistant to MccJ25, as a result of a mutation in an RNAP subunit gene, exhibits resistance to capistruin. The results indicate that the structural similarity of capistruin and MccJ25 reflects functional similarity and suggest that the functional target of capistruin, and possibly other threaded-lasso peptides, is bacterial RNAP.
authors.affiliation: (1)Department of Biochemistry and Molecular Biology and Waksman Institute of Microbiology, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Kuznedelov
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Semenova
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Knappe
authors.forename: Damir
authors.initials: D
authors.lastname: Mukhamedyarov
authors.forename: Aashish
authors.initials: A
authors.lastname: Srivastava
authors.forename: Sujoy
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Richard H
authors.initials: RH
authors.lastname: Ebright
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Marahiel
authors.forename: Konstantin
authors.initials: K
authors.lastname: Severinov
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D019117:Burkholderia / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D010455:Peptides; C533129:capistruin; D012321:DNA-Directed RNA Polymerases